Zolbetuximab Combination Therapy for Stomach Cancer
(ILUSTRO Trial)

Recruiting in Palo Alto (17 mi)

+17 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Astellas Pharma Global Development, Inc.

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This trial is testing zolbetuximab, a medicine that helps the immune system attack stomach and gastroesophageal cancers with a specific protein. It targets patients whose tumors have the CLDN18.2 protein, aiming to improve their response to treatment.

Eligibility Criteria

This trial is for adults with advanced or metastatic gastric or GEJ adenocarcinoma that tests positive for CLDN18.2. They should have a life expectancy of at least 12 weeks, meet specific lab criteria, and agree to contraception if applicable. Exclusions include severe allergies to similar drugs, recent immunosuppressive therapy, significant heart issues within the past 6 months, active infections requiring systemic treatment, other cancers needing treatment, and certain psychiatric or social conditions.

Inclusion Criteria

My cancer can be measured and was checked within the last 28 days.

I agree to use contraception for 6 months after my last treatment.

Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.

+36 more

Exclusion Criteria

Subject has known immediate or delayed hypersensitivity or contraindication to any component of study treatment.

I have not taken any immune-weakening medication, including steroids, in the last 14 days.

Subject has psychiatric illness or social situations that would preclude study compliance.

+18 more

Participant Groups

The study is testing Zolbetuximab's effectiveness alone and in combination with chemotherapy (mFOLFOX6) plus/minus Nivolumab or Pembrolizumab on tumor response rate and progression-free survival. It will also assess safety/tolerability, effects on CLDN18.2 expression levels, pharmacokinetics of all drugs involved, quality of life impacts from treatments provided.

5Treatment groups

Experimental Treatment

Group I: zolbetuximab (Cohort 1A)Experimental Treatment1 Intervention

Participants will be treated with zolbetuximab on a 21-day cycle in which zolbetuximab will be administered as a single agent every 3 weeks until disease progression, toxicity requiring cessation, start of another anti-cancer treatment or other treatment discontinuation criteria are met.

Group II: mFOLFOX6 plus zolbetuximab (Cohort 2)Experimental Treatment5 Interventions

Participants will be treated with zolbetuximab and mFOLFOX6 on a 42-day cycle in which zolbetuximab is administered on days 1 and 22, and mFOLFOX6 is administered on days 1, 15 and 29; however, for the first cycle, zolbetuximab will be administered on day 3 (instead of day 1) to allow for pharmacokinetic collection. Participants will receive up to 12 mFOLFOX6 treatments (4 cycles). Beginning at cycle 5, participants may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab for the remainder of the study per investigator's discretion. mFOLFOX6 treatment includes oxaliplatin: intravenous \[IV\] infusion, leucovorin: IV infusion, fluorouracil bolus: IV bolus, fluorouracil infusion: continuous IV infusion.

Group III: Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B)Experimental Treatment6 Interventions

Participants will be treated with zolbetuximab and mFOLFOX6, nivolumab on a 42-day cycle. Cohort 4A: Loading dose of zolbetuximab in combination with nivolumab and mFOLFOX6 on cycle 1 day 1, followed by zolbetuximab in combination with nivolumab and mFOLFOX6 q2w \[days 15 and 29\] (1 cycle = 6 weeks). Tolerability and safety of zolbetuximab in combination with nivolumab, mFOLFOX6 will be evaluated during the 3-week DLT assessment period. If cycle 1 dose is not tolerable, a lower dose of dose zolbetuximab in combination with nivolumab and mFOLFOX6 will be subsequently evaluated. Cohort 4B: Subjects will be treated with the combination of zolbetuximab, mFOLFOX6 and nivolumab at the dose deemed tolerable in Cohort 4A. Subjects will receive up to 12 mFOLFOX6 treatments (4 cycles). For Cohorts 4A and 4B, beginning at cycle 5, subjects may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab and nivolumab for the remainder of the study per investigator's discretion.

Group IV: Zolbetuximab in combination with FLOT (Cohort 5)Experimental Treatment6 Interventions

Participants will be treated with zolbetuximab \& FLOT for a total of eight 2-week cycles. 4 cycles preoperatively \& 4 cycles postoperatively 6-12 weeks after surgery. Preoperative: Participants will receive zolbetuximab loading dose on cycle 1 day 1, followed by FLOT on cycle 1 day 2. For cycles 2-4, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 \& FLOT on day 2. Post operative: Participants will receive zolbetuximab loading dose on cycle 5 day 1, followed by FLOT on cycle 5 day 2. For cycles 6-8, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 and FLOT on day 2. For participants who experience a DLT during preoperative treatment on the loading dose, the postoperative loading dose may be lowered.

Group V: Pembrolizumab plus zolbetuximab (Cohort 3A)Experimental Treatment2 Interventions

Participants will be treated with zolbetuximab and pembrolizumab on a 21-day cycle. Loading dose of zolbetuximab will be administered at cycle 1, day 1 followed by maintenance dose of zolbetuximab once every 3 weeks (Q3W). Pembrolizumab will be administered to 3 to 6 subjects at a intravenously on day 1 of every 21-day cycle and will be infused 1 hour after the zolbetuximab infusion is completed. Tolerability and safety of zolbetuximab in combination with pembrolizumab will be evaluated during the 3-week dose-limiting toxicity (DLT) assessment period. If this cycle 1 dose is not tolerable, a lower dose of zolbetuximab in combination with pembrolizumab will subsequently be evaluated.

Fluorouracil is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as 5-Fluorouracil for: